6-39878361-A-G

Variant names:

• chr6-39878361-A-G
• rs2504086
• NM_001201427.2:c.1361-43A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001201427.2(DAAM2):​c.1361-43A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.58 in 1,607,492 control chromosomes in the GnomAD database, including 272,058 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.58 (25802 hom., cov: 32)
  • Exomes 𝑓: 0.58 (246256 hom.)
• Consequence: DAAM2 NM_001201427.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.161
• Publications: 12 publications found

Genes affected

DAAM2 (HGNC:18143): (dishevelled associated activator of morphogenesis 2) Predicted to enable actin binding activity and small GTPase binding activity. Predicted to be involved in nervous system development and regulation of Wnt signaling pathway. Predicted to act upstream of or within determination of left/right symmetry. Located in extracellular exosome. [provided by Alliance of Genome Resources, Apr 2022]

DAAM2-AS1 (HGNC:40830): (DAAM2 antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.767 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001201427.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DAAM2	NM_001201427.2	MANE Select	c.1361-43A>G		intron	N/A	NP_001188356.1	Q86T65-3
	DAAM2	NM_015345.4		c.1361-43A>G		intron	N/A	NP_056160.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DAAM2	ENST00000274867.9	TSL:1 MANE Select	c.1361-43A>G		intron	N/A	ENSP00000274867.4	Q86T65-3
	DAAM2	ENST00000538976.5	TSL:1	c.1361-43A>G		intron	N/A	ENSP00000437808.1	Q86T65-4
	DAAM2	ENST00000491083.2	TSL:1	n.1507-43A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.580 AC: 88039 AN: 151822 Hom.: 25768 Cov.: 32

Gnomad AFR AF: 0.559

Gnomad AMI AF: 0.727

Gnomad AMR AF: 0.571

Gnomad ASJ AF: 0.578

Gnomad EAS AF: 0.788

Gnomad SAS AF: 0.692

Gnomad FIN AF: 0.612

Gnomad MID AF: 0.573

Gnomad NFE AF: 0.564

Gnomad OTH AF: 0.582

GnomAD2 exomes AF: 0.605 AC: 146265 AN: 241708 AF XY: 0.608

Gnomad AFR exome AF: 0.562

Gnomad AMR exome AF: 0.571

Gnomad ASJ exome AF: 0.579

Gnomad EAS exome AF: 0.799

Gnomad FIN exome AF: 0.607

Gnomad NFE exome AF: 0.572

Gnomad OTH exome AF: 0.573

GnomAD4 exome AF: 0.580 AC: 843764 AN: 1455552 Hom.: 246256 Cov.: 39 AF XY: 0.583 AC XY: 421604 AN XY: 723372

African (AFR) AF: 0.571 AC: 19043 AN: 33378

American (AMR) AF: 0.570 AC: 25076 AN: 44014

Ashkenazi Jewish (ASJ) AF: 0.575 AC: 14865 AN: 25862

East Asian (EAS) AF: 0.737 AC: 29154 AN: 39554

South Asian (SAS) AF: 0.678 AC: 57993 AN: 85558

European-Finnish (FIN) AF: 0.600 AC: 31899 AN: 53134

Middle Eastern (MID) AF: 0.600 AC: 3448 AN: 5742

European-Non Finnish (NFE) AF: 0.565 AC: 626602 AN: 1108190

Other (OTH) AF: 0.594 AC: 35684 AN: 60120

GnomAD4 genome AF: 0.580 AC: 88121 AN: 151940 Hom.: 25802 Cov.: 32 AF XY: 0.583 AC XY: 43323 AN XY: 74254

African (AFR) AF: 0.560 AC: 23184 AN: 41432

American (AMR) AF: 0.571 AC: 8720 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.578 AC: 2007 AN: 3472

East Asian (EAS) AF: 0.787 AC: 4067 AN: 5166

South Asian (SAS) AF: 0.691 AC: 3314 AN: 4798

European-Finnish (FIN) AF: 0.612 AC: 6451 AN: 10542

Middle Eastern (MID) AF: 0.582 AC: 171 AN: 294

European-Non Finnish (NFE) AF: 0.564 AC: 38305 AN: 67930

Other (OTH) AF: 0.587 AC: 1239 AN: 2112

Alfa AF: 0.572 Hom.: 68452

Bravo AF: 0.578

Asia WGS AF: 0.737 AC: 2567 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.21
DANN	Benign	0.67
PhyloP100		0.16
Mutation Taster		=21/79	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs2504086; hg19: chr6-39846137;